Loss of alpha-conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum.
Loss of alpha-conotoxinMII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum.
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帕金森病纹状体中 α-芋螺毒素 MII 和 A85380 敏感烟碱受体的丧失。
DOI：
10.1111/j.1471-4159.2004.02177.x
复制
发表时间：
2004
影响因子：
4.7
通讯作者：
McIntosh,JM
中科院分区：
文献类型：
--
作者：
Quik,M;Bordia,T;Forno,L;McIntosh,JM
啮齿动物和猴子纹状体中存在多种烟碱受体，α-芋螺毒素MII敏感位点选择性定位在纹状体中，并且在黑质纹状体损伤后其数量优先下降。在这里，我们报告了人类对照和帕金森病纹状体中存在 125I-α-芋螺毒素 MII 和 α-芋螺毒素 MII 敏感的 125I-表巴替丁烟碱受体。 125I-α-芋螺毒素 MII 与具有烟碱配体特征的对照纹状体结合，尽管位点数量比啮齿动物和猴子中的约少五倍。 α-芋螺毒素 MII 与 125 I-依巴替丁的竞争分析表明，毒素敏感位点包含人纹状体中约 15% 的烟碱受体。在帕金森病尾状核中，125I-α-芋螺毒素 MII 位点下降约 50%，多巴胺转运蛋白也有类似下降。在壳核中，多巴胺转运蛋白的损失显着增加（80-90%），但 125I-α-芋螺毒素 MII 位点仅减少 50-60%，α-芋螺毒素 MII 敏感的 125I-epibatidine 位点、125I-epibatidine（多个）位点和 125I-A85380（含 β2）烟碱受体也相应下降。与烟碱位点相比，转运蛋白的损失更大，这表明只有烟碱受体亚群位于人类纹状体多巴胺能神经元的突触前。帕金森病纹状体烟碱受体和多巴胺转运蛋白变化之间的相关性分析表明，α-芋螺毒素MII敏感的125I-epibatidine位点（低亲和力位点）、125I-A85380和125I-epibatidine位点部分位于多巴胺能末端。总之，这些结果表明，人类纹状体中存在 α-芋螺毒素 MII 敏感位点，并且存在高亲和力和低亲和力亚型，这些亚型在帕金森病中均减少。
Multiple nicotinic receptors are present in rodent and monkey striatum, with a selective localization of α‐conotoxinMII‐sensitive sites in the striatum and preferential declines in their numbers after nigrostriatal damage. Here we report the presence of125I‐α‐conotoxinMII and α‐conotoxinMII‐sensitive125I‐epibatidine nicotinic receptors in human control and Parkinson's disease striatum.125I‐α‐ConotoxinMII bound to control striatum with the characteristics of a nicotinic receptor ligand although the number of sites was approximately fivefold lower than in rodent and monkey. Competition analyses of α‐conotoxinMII with125I‐epibatidine showed that toxin‐sensitive sites comprised ≈15% of nicotinic receptors in human striatum. In Parkinson's disease caudate, there was a ≈50% decline in125I‐α‐conotoxinMII sites with a similar decline in the dopamine transporter. In putamen, there were substantially greater losses of the dopamine transporter (80–90%) but only 50–60% decreases in125I‐α‐conotoxinMII sites with corresponding declines in α‐conotoxinMII‐sensitive125I‐epibatidine sites,125I‐epibatidine (multiple) sites and125I‐A85380 (β2‐containing) nicotinic receptors. The greater loss of the transporter compared with nicotinic sites suggests that only a subpopulation of nicotinic receptors is located pre‐synaptically on striatal dopaminergic neurons in man. Correlation analyses between changes in nicotinic receptors and the dopamine transporter in Parkinson's disease striatum suggest that α‐conotoxinMII‐sensitive125I‐epibatidine sites (low‐affinity sites),125I‐A85380 and125I‐epibatidine sites are localized in part to dopaminergic terminals. In summary, these results show that α‐conotoxinMII‐sensitive sites are present in human striatum and that there are high‐ and low‐affinity subtypes which are both decreased in Parkinson's disease.
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DOI：
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发表时间：
1983
期刊：
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
SAUNDERS, RR;WACHTER, J;SPRADLIN, JE
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2.7
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2.7
作者：
LAZAR, RM;DAVISLANG, D;SANCHEZ, L
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影响因子：
2.7
作者：
LAZAR, R
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